Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Calibra Lab at DIAN Diagnostics, Hangzhou, China.
Front Immunol. 2023 Sep 27;14:1254155. doi: 10.3389/fimmu.2023.1254155. eCollection 2023.
Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied.
Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls.
Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism.
Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.
与人类免疫缺陷病毒 1 型（HIV-1）感染相关的慢性代谢变化以及针对抗逆转录病毒治疗（ART）的反应仍未确定。此外，HIV 引起的代谢功能障碍与长期接受治疗的个体中的免疫炎症之间的联系尚未得到充分研究。
在 47 名 HIV 感染者中评估了非靶向代谢组学和炎症细胞因子水平，包括 22 名免疫反应者（IRs）和 25 名无反应者（INRs），在 ART 前后进行评估。IRs 和 INRs 按年龄、性别、基线病毒载量和基线 CD4+T 细胞计数进行匹配。还纳入了另外 25 名年龄匹配的未感染健康个体作为对照。
在本研究中检测到的 770 种血浆化合物中，脂质、核苷酸和生物源氨基酸在 HIV 感染者和健康对照者之间存在显著变化。主成分分析（PCA）和随机森林（RF）模型表明，选定代谢物的水平可以将 HIV 感染者与健康对照者区分开来。然而，我们患者中鉴定的代谢物谱相似，只有三种代谢物，麦芽糖四糖、N，N-二甲基-5-氨基戊酸和癸二烯二酸（C10：2-DC），在长期 ART 后 IRs 和 INRs 之间有所不同。途径富集分析结果表明，HIV 感染后嘧啶代谢、鞘脂代谢和嘌呤代谢紊乱，即使在抑制性 ART 下，这些变化也未恢复到健康对照者的正常水平。代谢-免疫网络的相关性分析表明，白细胞介素（IL）-10、D-二聚体、血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和 TNF-RII 与大多数显著改变的脂质和氨基酸代谢物呈正相关，但与核苷酸代谢物呈负相关。
无论免疫恢复状况如何，HIV 感染者在接受 ART 前后都观察到许多代谢物的显著变化。即使在长期 ART 后，HIV 感染中脂质和核苷酸的代谢谱紊乱也未恢复正常。这些变化与慢性非艾滋病事件的修饰细胞因子和生物标志物相关，需要尝试除 ART 以外的干预措施。
